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Combos Explored to Enhance CLL Outcomes

Gina Columbus @ginacolumbusonc
Published: Friday, Jul 28, 2017

The success of ibrutinib (Imbruvica) has had a significant impact across several populations of patients with chronic lymphocytic leukemia (CLL). However, not all patients respond, and ibrutinib combinations and other novel regimens are being explored to improve outcomes, said Julio Chavez, MD.

For example, findings from the phase III GENUINE trial, which were presented at the 2017 ASCO Annual Meeting, showed that the combination of ublituximab (TG-1101) and ibrutinib demonstrated an objective response rate of 78% for patients with previously treated high-risk CLL.

A separate ongoing, multicenter, open-label, prospective phase III study is exploring the efficacy and safety of obinutuzumab (Gazyva) plus venetoclax (Venclexta) versus obinutuzumab and chlorambucil in patients with CLL (NCT02242942). If positive, Chavez adds, it could lead to another frontline treatment option for patients.

Chavez, who works in the Department of Malignant Hematology at Moffitt Cancer Center, discussed the current state of CLL and emerging regimens moving through the pipeline during the 2017 OncLive® State of the Science SummitTM on Hematologic Malignancies. In an interview at the meeting, he shared his insight on ibrutinib’s benefits and challenges, and emerging combinations in CLL.

OncLive: What did you focus on in your lecture on CLL?

Chavez: CLL is the most common chronic leukemia in the United States. I focused on the new treatments available for this condition, including novel agents, and also on the efficacy and toxicity of potential combinations for future treatments on these patients. 

What game-changing results have we seen with ibrutinib? Also, what do you do when patients fail on ibrutinib?

Ibrutinib has changed the landscape of treatment entirely for CLL. It is an oral agent that is generally well tolerated; however, there are some toxicities we should keep in mind, like increased bleeding, atrial fibrillation, or infections. Those are manageable, but we have to keep in mind that there are potential comorbidities.

The efficacy of ibrutinib is impressive in basically all settings—in high-risk patients, those with 17p deletion, elderly patients, those with treatment-naïve disease, and relapsed/refractory patients. The success has been remarkable in CLL. 

However, there are some issues. As I mentioned before, the CR rates are low—less than 10%. It doesn’t increase with combination therapy, whether we add rituximab (Rituxan) or whether we had bendamustine and rituximab or chemotherapy. It doesn’t increase much of the CR rates. It has been noted that deeper remissions are associated with good outcomes in patients with CLL.

The other problem is that patients discontinue treatment on ibrutinib for several reasons. Whether it is because of toxicity or disease progression, the outcomes are not good. Especially for patients who have progression of disease in CLL, there are alternatives but we have to be careful what to choose.

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